Cancers of the head and neck region are among the leading causes of cancer-related mortalities worldwide. Oral leukoplakia and erythroplakia are identified as precursor lesions to malignancy.

Patients cured of an initial primary head and neck cancer are also susceptible to developing second primary tumors due to cancerization of their mucosal field.

Multi-step acquisition of genetic mutations leading to tumorigenesis and development of invasive cancer has been previously described. Recently, whole exome sequencing of tumor specimens has helped to identify driver mutations in this disease.

For these reasons, chemoprevention or the use of systemic or biologic agents to prevent carcinogenesis is an attractive concept in head and neck cancers. Nonetheless, despite extensive clinical research in this field over the past couple decades, no standard of care option has emerged.

This review article reports on targeted interventions that have been attempted in clinical trials to date, and focuses on novel molecular pathways and drugs in development that are worthy of being tested for this indication as part of future endeavors.